The present invention relates to a protein having sugar-transporting activity and a DNA coding for said protein.
Glucose, a main energy source in cranial nerve tissue has a low molecular weight of 180 but cannot pass through cell membrane rapidly because it is a polar molecule. Therefore, glucose is incorporated into cells through glucose transporters, sugar-transporting proteins that are specifically present in the form of cell membrane.
At present, as the glucose transporters, there are known those of two types, i.e., energy-dependent Na+/glucose symport type for active transport of glucose against glucose concentration gradient, and facilitated diffusion transport type for transport dependent only on the difference between intracellular and extracellular glucose concentrations. It is considered that the facilitated diffusion transport type performs the principal role in cranial nerve tissue, and there have been reported GLUT1 which is present in hemoendothelial cells and participates in sugar transport in blood-brain barrier (J. Biol. Chem., 263, 15245 (1988)) and GLUT3 which is considered to transport glucose passed through blood-brain barrier, to nerve cells (J. Biol. Chem., 265, 18035 (1990)).
There are, for example, the following reports indicating the relation between neuropathy and the functional and expression abnormalities of glucose transporters: the partial deficiency of GLUT1 causes convulsion and psychogenetic retardation (N. Engl. J. Med., 325, 703 (1991)); the possibility of the functional abnormality of GLUT3 is suggested in the case of Parkinson""s disease (Ann. Neurol., 32, S88 (1992)); and the expression of GLUT3 is markedly accelerated in a blood vessel in tumor (Cancer Res., 52, 3972 (1992)).
The present inventors earnestly investigated proteins coded for by genes that had been expressed specifically in human brain tissue, and consequently succeeded in isolating a novel protein (hereinafter referred to as HUCEP-8) and a gene coding for this protein (hereinafter referred to as hucep-8). The present inventors found that this HUCEP-8 transports monosaccharides such as glucose into cells, whereby the present invention has been accomplished.
That is, the present invention provides (1) (a) a novel protein HUCEP-8 having the amino acid sequence shown as SEQ ID NO: 1, or (b) a protein having an amino acid sequence formed by deletion, substitution or addition of one or more amino acids in the amino acid sequence shown as SEQ ID NO: 1, and having sugar-transporting activity; (2) a gene coding for either of the proteins described in (1); (3) (c) a DNA having the base sequence shown as SEQ ID NO: 2, or (d) a DNA which hybridizes with the DNA of SEQ ID NO: 2 under stringent conditions and codes for a protein having sugar-transporting activity; (4) a method for screening compounds capable of enhancing or inhibiting sugar-transporting activity, characterized by using the protein described in (1); (5) a method for screening compounds capable of enhancing or inhibiting sugar-transporting activity, characterized by using the gene described in (2) or (3); (6) a method for screening compounds capable of accelerating or inhibiting the transcription of the gene described in (2) or (3); (7) a method for screening compounds capable of accelerating or inhibiting the translocation of either of the protein described in (1); (8) a compound or a salt thereof, which is obtained by conducting the screening method described in (4), (5), (6) or (7); and (9) an antibody against the protein described in (1).